Novel Macromolecular Antioxidants Comprising Differing Antioxidant Moieties: Structures, Methods of Making and Using The Same

ABSTRACT

Described are antioxidant macromolecules and methods of making and using same.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.12/319,282 filed Jan. 5, 2009, which is a continuation of InternationalApplication No. PCT/US2007/015177, which designated the United Statesand was filed on Jun. 29, 2007, published in English, which claims thebenefit of U.S. Provisional Application No. 60/818,876, filed on Jul. 6,2006. The entire teachings of the above applications are incorporatedherein by reference.

BACKGROUND OF THE INVENTION

Antioxidants are employed to prevent oxidation in a wide range ofmaterials, for example, plastics, elastomers, lubricants, petroleumbased products (lubricants, gasoline, aviation fuels, and engine oils),cooking oil, cosmetics, processed food products, and the like. Whilemany antioxidants exist, there is a continuing need for new antioxidantsthat have improved properties.

SUMMARY OF THE INVENTION

The present invention relates to antioxidant macromolecules that ingeneral have improved antioxidant properties.

In one embodiment the present invention is directed to compoundsrepresented Structural Formula I or II:

wherein:

R is:

A in each occurrence, independently is —O—, —NH—, —S—, —C(O)—, —C(O)NH—,—NHC(O)—, —C(O)O—, —OC(O)—, —CH═N— or —N═CH—;

A′ in each occurrence, independently is a bond, —O—, —NH—, —S—, —C(O)—,—C(O)NH—, —NHC(O)—, —C(O)O—, —OC(O)—, —CH═N— or —N═CH—;

B in each occurrence, independently is a bond or an optionallysubstituted alkylene group;

C in each occurrence independently is —H, an optionally substitutedalkylene group or

R₁ and R₂ in each occurrence, independently is an optionally substitutedalkyl, optionally substituted aryl or optionally substituted aralkyl;

Z in each occurrence, independently is a bond, an optionally substitutedalkylene group, —(CH₂)₁NHC(O)(CH₂)₁—, —(CH₂)₁C(O)NH(CH₂)₁—,—(CH₂)₁C(O)O(CH₂)₁—, —(CH₂)₁OC(O)(CH₂)₁—, —(CH₂)₁CH═N(CH₂)₁—,—(CH₂)₁N═CH(CH₂)₁—, —(CH₂)₁NH(CH₂)₁—, —(CH₂)₁S(CH₂)₁—, —(CH₂)₁O(CH₂)₁—or —(CH₂)₁C(O)(CH₂)₁—;

i in each occurrence, independently is 0, 1, 2 or 3;

j in each occurrence, independently is 0, 1, 2, 3 or 4;

l in each occurrence, independently is 0 or a positive integer from 1 to12; and

s is a positive integer from 1 to 6.

In another embodiment the present invention is directed to compoundsrepresented Structural Formula III or IV:

wherein:

A is —C(O)NR′—, —NR′C(O)—, —NR′—, —CR′═N—, —C(O)—, —C(O)O—, —OC(O)—,—O—, —S—, —C(O)OC(O)— or a bond;

each R′ is independently —H or optionally substituted alkyl;

each R** is independently an optionally substituted alkyl, optionallysubstituted aryl, optionally substituted alkoxycarbonyl, optionallysubstituted ester, —OH, —NH₂, —SH, or

each R₁ and R₂ is independently an optionally substituted alkyl,optionally substituted aryl, optionally substituted alkoxycarbonyl,optionally substituted ester, —OH, —NH₂ or —SH;

X is —C(O)O—, —OC(O)—, —C(O)NR′—, —NR′C(O)—, —NR′—, —CH═N—, —C(O)—, —O—,—S—, —NR′— or —C(O)OC(O)—;

M is —H, an alkyl or

each n is independently a positive integer from 1 to 6;

each m is independently 0 or a positive integer from 1 to 6; and

each s, q and u are independently integers from 0 to 4.

R—Z—(CH₂)_(k)—Z—R

wherein R is:

A is —C(O)NR′—, —NR′C(O)—, —NR′—, —CR′═N—, —C(O)—, —C(O)O—, —OC(O)—,—O—, —S—, —C(O)OC(O)— or a bond;

Z in each occurrence, independently is a bond, an optionally substitutedalkylene group, —(CH₂)₁NHC(O)(CH₂)₁—, —(CH₂)₁C(O)NH(CH₂)₁—,—(CH₂)₁C(O)O(CH₂)₁—, —(CH₂)₁OC(O)(CH₂)₁—, —(CH₂)₁CH═N(CH₂)₁—,—(CH₂)₁N═CH(CH₂)₁—, —(CH₂)₁NH(CH₂)₁—, —(CH₂)₁S(CH₂)₁—, —(CH₂)₁O(CH₂)₁—or —(CH₂)₁C(O)(CH₂)₁—;

each R′ is independently —H or optionally substituted alkyl;

each R** is independently an optionally substituted alkyl, optionallysubstituted aryl, optionally substituted alkoxycarbonyl, optionallysubstituted ester, —OH, —NH₂, —SH, or

each R₁ and R₂ is independently an optionally substituted alkyl,optionally substituted aryl, optionally substituted alkoxycarbonyl,optionally substituted ester, —OH, —NH₂ or —SH;

X is —C(O)O—, —OC(O)—, —C(O)NR′—, —NR′C(O)—, —NR′—, —CR′═N—, —C(O)—,—O—, —S—, —NR′— or —C(O)OC(O)—;

each M′ is independently —H, alkyl, or

each n is independently a positive integer from 1 to 6;

each m is independently 0 or a positive integer from 1 to 6;

l in each occurrence, independently is 0 or a positive integer from 1 to12; and

k in each occurrence independently is a positive integer from 1 to 12;

each q is independently an integer from 0 to 3;

each s, and u are independently integers from 0 to 4; and

r is an integer from 0 to 4.

In another embodiment the present invention is directed to methods ofinhibiting oxidation in an oxidizable material comprising combining theoxidizable material with a compound described herein.

In another embodiment the present invention is directed to methods ofinhibiting oxidation in an oxidizable material comprising combining theoxidizable material with a composition comprising a compound describedherein.

In another embodiment the present invention is a method of making acompound described herein.

In certain embodiments, the antioxidant macromolecules of the presentinvention can have enhanced antioxidant activity and better thermalstability compared to commercially available antioxidants.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects, features and advantages of theinvention will be apparent from the following more particulardescription of preferred embodiments of the invention, as illustrated inthe accompanying drawings in which like reference characters refer tothe same parts throughout the different views. The drawings are notnecessarily to scale, emphasis instead being placed upon illustratingthe principles of the invention.

FIG. 1 is an IR spectrum of a tyramine based product of the presentinvention.

FIG. 2 is a UV spectrum of a tyramine based product of the presentinvention.

FIG. 3 is a ¹H NMR spectrum of a tyramine based product of the presentinvention.

DETAILED DESCRIPTION OF THE INVENTION

A description of preferred embodiments of the invention follows.

In certain embodiments the compounds of the present invention compriseat least one sterically hindered groups such as phenol groups(antioxidant moiety). Sterically hindered, as used herein means that thesubstituent group (e.g., bulky alkyl group) on a ring carbon atomadjacent (or alternatively para) to a ring carbon atom substituted witha phenolic hydroxy group (or thiol or amine group), is large enough tosterically hinder the phenolic hydroxy group (or thiol or amine groups).This steric hindrance, in certain embodiments results in more labile orweak bonding between the oxygen and the hydrogen (or sulfur or nitrogenand hydrogen) and in turn enhances the stability and antioxidantactivity (proton donating activity) of the sterically hinderedantioxidant.

Repeat units of the antioxidants of the invention include substitutedbenzene molecules. Some of these benzene molecules are typically basedon phenol or a phenol derivative, such that they have at least onehydroxyl or ether functional group. In certain embodiments, the benzenemolecules have a hydroxyl group. The hydroxyl group can be a freehydroxyl group and can be protected or have a cleavable group attachedto it (e.g., an ester group). Such cleavable groups can be releasedunder certain conditions (e.g., changes in pH), with a desired shelflife or with a time-controlled release (e.g., measured by thehalf-life), which allows one to control where and/or when an antioxidantcan exert its antioxidant effect. The repeat units can also includeanalogous thiophenol and aniline derivatives, e.g., where the phenol —OHcan be replaced by —SH, —NH—, and the like.

Substituted benzene repeat units of an antioxidant of the invention arealso typically substituted with a bulky alkyl group or ann-alkoxycarbonyl group. In certain embodiments, the benzene monomers aresubstituted with a bulky alkyl group. In certain other embodiments, thebulky alkyl group is located ortho or meta to a hydroxyl group on thebenzene ring, typically ortho. A “bulky alkyl group” is defined hereinas an alkyl group that is branched alpha- or beta- to the benzene ring.In certain other embodiments, the alkyl group is branched alpha to thebenzene ring. In certain other embodiments, the alkyl group is branchedtwice alpha to the benzene ring, such as in a tert-butyl group. Otherexamples of bulky alkyl groups include isopropyl, 2-butyl, 3-pentyl,1,1-dimethylpropyl, 1-ethyl-1-methylpropyl and 1,1-diethylpropyl. Incertain other embodiments, the bulky alkyl groups are unsubstituted, butthey can be substituted with a functional group that does not interferewith the antioxidant activity of the molecule. Straight chainedalkoxylcarbonyl groups include methoxycarbonyl, ethoxycarbonyl,n-propoxycarbonyl, n-butoxycarbonyl and n-pentoxycarbonyl.N-propoxycarbonyl is a preferred group. Similar to the bulky alkylgroups, n-alkoxycarbonyl groups are optionally substituted with afunctional group that does not interfere with the antioxidant activityof the molecule.

In certain embodiments for compounds represented by Structural Formula Ior II or narrower embodiments thereof:

R is:

In other embodiments, R is:

In other embodiments, R is:

In other embodiments, R is:

In other embodiments, R is:

A in each occurrence, independently is —O—, —NH—, —S—, —C(O)—, —C(O)NH—,—NHC(O)—, —C(O)O—, —OC(O)—, —CH═N— or —N═CH—. In other embodiments, A ineach occurrence, independently is —C(O)O— or —OC(O)—. In otherembodiments A in each occurrence, independently is —C(O)NH— or —NHC(O)—;

A′ in each occurrence, independently is a bond, —O—, —NH—, —S—, —C(O)—,—C(O)NH—, —NHC(O)—, —C(O)O—, —OC(O)—, —CH═N— or —N═CH—. In otherembodiments, A′ is a bond;

B in each occurrence, independently is a bond or an optionallysubstituted alkylene group. In certain embodiments both B groups are aC2 alkylene group. In certain embodiments one B groups is a C2 alkylenegroup, and the other is a bond;

C in each occurrence independently is —H, an optionally substitutedalkylene group or

In certain embodiments C is a sterically hindered antioxidant moietyrepresented by the following structural formula:

R₁ and R₂ in each occurrence, independently is an optionally substitutedalkyl, optionally substituted aryl or optionally substituted aralkyl. Inother embodiments, R₁ and R₂ in each occurrence, independently is anoptionally substituted alkyl. In other embodiments, R₁ is a C1-C6 alkyl.In other embodiments R₁ is a tert-butyl;

Z in each occurrence, independently is a bond, an optionally substitutedalkylene group, —(CH₂)₁NHC(O)(CH₂)₁—, —(CH₂)₁C(O)NH(CH₂)₁—,—(CH₂)₁C(O)O(CH₂)₁—, —(CH₂)₁OC(O)(CH₂)₁—, —(CH₂)₁CH═N(CH₂)₁—,—(CH₂)₁N═CH(CH₂)₁—, —(CH₂)₁NH(CH₂)₁—, —(CH₂)₁S(CH₂)₁—, —(CH₂)₁O(CH₂)₁—or —(CH₂)₁C(O)(CH₂)₁—. In other embodiments, Z in each occurrence,independently is a bond, an optionally substituted alkylene group,—(CH₂)₁NHC(O)(CH₂)₁—, —(CH₂)₁C(O)NH(CH₂)₁—, —(CH₂)₁C(O)O(CH₂)₁—,—(CH₂)₁OC(O)(CH₂)₁—, —(CH₂)₁O(CH₂)₁— or —(CH₂)₁C(O)(CH₂)₁—. In otherembodiments, Z in each occurrence, independently is a bond, anoptionally substituted alkylene group, —(CH₂)₁C(O)O(CH₂)₁—,—(CH₂)₁OC(O)(CH₂)₁—, —(CH₂)₁O(CH₂)₁— or —(CH₂)₁C(O)(CH₂)₁—. In otherembodiments, Z in each occurrence, independently is —(CH₂)₁C(O)O(CH₂)₁—or —(CH₂)₁OC(O)(CH₂)₁—. In other embodiments, Z is —(CH₂)₁O(CH₂)₁—. Inother embodiments, Z is —(CH₂)₁C(O)(CH₂)₁—;

i in each occurrence, independently is 0, 1, 2 or 3. In otherembodiments, i in each occurrence, independently is 0, 1, or 2. In otherembodiments, i is 0 or 1;

j in each occurrence, independently is 0, 1, 2, 3 or 4. In otherembodiments, j in each occurrence, independently is 0, 1 or 2. In otherembodiments j is 2.

1 in each occurrence, independently is 0 or a positive integer from 1 to12. In other embodiments, l in each occurrence independently is 0 or apositive integer from 1 to 6. In other embodiments 1 in each occurrenceindependently is 0 or a positive integer from 1 to 3;

s is a positive integer from 1 to 6. In other embodiments, s is 3; and

n and m in each occurrence, independently is 0 or a positive integerfrom 1 to 12. In other embodiments, n and m in each occurrence,independently is 0 or a positive an integer from 1 to 6. In otherembodiments, n is an integer from 0 to 4. In other embodiments both nand m are 2. In other embodiments n is 0 and m is 2.

In certain embodiments of the present invention the compound isrepresented by structural formula I.

In certain embodiments of the present invention the compound isrepresented by structural formula II. In certain embodiments of thepresent invention structural formula II is represented by the followingstructural formula:

and the remainder of the variables are as described above.

In a first embodiment for compounds of Structural formula I and II:

R is:

wherein:

n and m in each occurrence, independently is 0 or a positive integerfrom 1 to 12; and the remainder of the variables are as described above.

In a second embodiment for compounds of Structural formula I and II:

R₁ and R₂ in each occurrence, independently is an optionally substitutedalkyl; and

i and j in each occurrence, independently is 0, 1 or 2 and the remainderof the variables are as described above in the first embodiment.

In a third embodiment for compounds of Structural formula I and II:

R is:

wherein:

n and m in each occurrence, independently is 0 or a positive an integerfrom 1 to 6; and

i is 0 or 1 and the remainder of the variables are as described above inthe second embodiment.

In a fourth embodiment for compounds of Structural formula I and II:

Z in each occurrence, independently is a bond, an optionally substitutedalkylene group, —(CH₂)₁NHC(O)(CH₂)₁—, —(CH₂)₁C(O)NH(CH₂)₁—,—(CH₂)₁C(O)O(CH₂)₁—, —(CH₂)₁OC(O)(CH₂)₁—, —(CH₂)₁O(CH₂)₁— or—(CH₂)₁C(O)(CH₂)₁—; and

l in each occurrence independently is 0 or a positive integer from 1 to6 and the remainder of the variables are as described above in the thirdembodiment.

In a fifth embodiment for compounds of Structural formula I and II:

A in each occurrence, independently is —C(O)O— or —OC(O)— and theremainder of the variables are as described above in the fourthembodiment.

Alternatively, A in each occurrence, independently is —C(O)NH— or—NHC(O)— and the remainder of the variables are as described above inthe fourth embodiment.

In a sixth embodiment for compounds of Structural formula I and II:

R is:

wherein:

n is an integer from 0 to 4; and

R₁ is a C1-C6 alkyl and the remainder of the variables are as describedabove in the fifth embodiment.

In a seventh embodiment for compounds of Structural formula I and II:

Z in each occurrence, independently is a bond, an optionally substitutedalkylene group, —(CH₂)₁C(O)O(CH₂)₁—, —(CH₂)₁OC(O)(CH₂)₁—,—(CH₂)₁O(CH₂)₁— or —(CH₂)₁C(O)(CH₂)₁—; and

l in each occurrence independently is 0 or a positive integer from 1 to3

In certain embodiments for compounds represented by Structural FormulaIII or IV or narrower embodiments thereof:

A is —C(O)NR′—, —NR′C(O)—, —NR′—, —CR′═N—, —C(O)—, —C(O)O—, —OC(O)—,—O—, —S—, —C(O)OC(O)— or a bond. In other embodiments, A is —C(O)O—,—OC(O)—, —C(O)NH—, —NHC(O)—, —NH—, —O— or —C(O)—. In other embodiments,A is —C(O)NH— or —NHC(O)—. In certain embodiments, A is not —C(O)O—,—OC(O)—, —O— or —NH—. In various embodiments, A is —OC(O)—. In anotherembodiment, A is —C(O)O—. In another embodiment, A is —C(O)NH—. Inanother embodiment, A is —NHC(O)—. In another embodiment, A is —NH—. Inanother embodiment, A is —CH═N—. In another embodiment, A is —C(O)—. Inanother embodiment, Z is —O—. In another embodiment, A is —C(O)OC(O)—.In another embodiment, A is a bond;

Z in each occurrence, independently is a bond, an optionally substitutedalkylene group, —(CH₂)₁NHC(O)(CH₂)₁—, —(CH₂)₁C(O)NH(CH₂)₁—,—(CH₂)₁C(O)O(CH₂)₁—, —(CH₂)₁OC(O)(CH₂)₁—, —(CH₂)₁CH═N(CH₂)₁—,—(CH₂)₁N═CH(CH₂)₁—, —(CH₂)₁NH(CH₂)₁—, —(CH₂)₁S(CH₂)₁—, —(CH₂)₁O(CH₂)₁—or —(CH₂)₁C(O)(CH₂)₁—. In other embodiments, Z in each occurrence,independently is a bond, an optionally substituted alkylene group,—(CH₂)₁NHC(O)(CH₂)₁—, —(CH₂)₁C(O)NH(CH₂)₁—, —(CH₂)₁C(O)O(CH₂)₁—,—(CH₂)₁OC(O)(CH₂)₁—, —(CH₂)₁O(CH₂)₁— or —(CH₂)₁C(O)(CH₂)₁—. In otherembodiments, Z in each occurrence, independently is a bond, anoptionally substituted alkylene group, —(CH₂)₁C(O)O(CH₂)₁—,—(CH₂)₁OC(O)(CH₂)₁—, —(CH₂)₁O(CH₂)₁— or —(CH₂)₁C(O)(CH₂)₁—. In otherembodiments, Z in each occurrence, independently is —(CH₂)₁C(O)O(CH₂)₁—or —(CH₂)₁OC(O)(CH₂)₁—. In other embodiments, Z is —(CH₂)₁O(CH₂)₁—. Inother embodiments, Z is —(CH₂)₁C(O)(CH₂)₁—;

Each R′ is independently —H or optionally substituted alkyl. In certainother embodiments R′ is —H or an alkyl group. In certain otherembodiments R′ is —H or a C1-C10 alkyl group. In certain otherembodiments R′ is —H.

Each R is independently an optionally substituted alkyl, optionallysubstituted aryl, optionally substituted alkoxycarbonyl, optionallysubstituted ester, —OH, —NH₂, —SH, or

In certain other embodiments, each R is independently an optionallysubstituted alkyl or optionally substituted alkoxycarbonyl. In certainother embodiment each R is independently an alkyl or alkoxycarbonyl. Incertain other embodiments each R is independently a C1-C6 alkyl or aC1-C6 alkoxycarbonyl. In certain other embodiments each R isindependently tert-butyl or propoxycarbonyl. In certain otherembodiments each R is independently an alkyl group. In certainembodiments each R is independently a bulky alkyl group. Suitableexamples of bulky alkyl groups include butyl, sec-butyl, tert-butyl,2-propyl, 1,1-dimethylhexyl, and the like. In certain embodiments each Ris tert-butyl. In certain embodiments at least one R adjacent to the —OHgroup is a bulky alkyl group (e.g., butyl, sec-butyl, tert-butyl,2-propyl, 1,1-dimethylhexyl, and the like). In certain other embodimentsboth R groups adjacent to —OH are bulky alkyl groups (e.g., butyl,sec-butyl, tert-butyl, 2-propyl, 1,1-dimethylhexyl, and the like). Inanother embodiment, both R groups are tert-butyl. In another embodiment,both R groups are tert-butyl adjacent to the OH group.

Each R₁ is independently an optionally substituted alkyl, optionallysubstituted aryl, optionally substituted alkoxycarbonyl, optionallysubstituted ester, —OH, —NH₂ or —SH. In certain other embodiments, eachR₁ is independently an optionally substituted alkyl or optionallysubstituted alkoxycarbonyl. In certain other embodiment each R₁ isindependently an alkyl or alkoxycarbonyl. In certain other embodimentseach R₁ is independently a C1-C6 alkyl or a C1-C6 alkoxycarbonyl. Incertain other embodiments each R₁ is independently tert-butyl orpropoxycarbonyl. In certain other embodiments each R₁ is independentlyan alkyl group. In certain embodiments each R₁ is independently a bulkyalkyl group. Suitable examples of bulky alkyl groups include butyl,sec-butyl, tert-butyl, 2-propyl, 1,1-dimethylhexyl, and the like. Incertain embodiments each R₁ is tert-butyl. In certain embodiments atleast one R₁ adjacent to the —OH group is a bulky alkyl group (e.g.,butyl, sec-butyl, tert-butyl, 2-propyl, 1,1-dimethylhexyl, and thelike). In certain other embodiments both R₁ groups adjacent to —OH arebulky alkyl groups (e.g., butyl, sec-butyl, tert-butyl, 2-propyl,1,1-dimethylhexyl, and the like). In another embodiment, both R₁ groupsare tert-butyl. In another embodiment, both R₁ groups are tert-butyladjacent to the OH group.

Each R₂ is independently an optionally substituted alkyl, optionallysubstituted aryl, optionally substituted alkoxycarbonyl, optionallysubstituted ester, —OH, —NH₂ or —SH. In certain other embodiments, eachR₂ is independently an optionally substituted alkyl or optionallysubstituted alkoxycarbonyl. In certain other embodiment each R₂ isindependently an alkyl or alkoxycarbonyl. In certain other embodiments,each R₂ is independently an optionally substituted alkyl. In certainother embodiment each R₂ is independently an alkyl. In certain otherembodiments each R₂ is independently a C1-C10 alkyl. In certain otherembodiments each R₂ is independently a C1-C6 alkyl. In certain otherembodiments each R₂ is independently a bulky alkyl group or a straightchained alkyl group. In certain other embodiments each R₂ isindependently methyl, ethyl, propyl, butyl, sec-butyl, tert-butyl,2-propyl or 1,1-dimethylhexyl. In certain embodiments each R₂ is methylor tert-butyl.

X is —C(O)O—, —OC(O)—, —C(O)NR′—, —NR′C(O)—, —NR′—, —CH═N—, —C(O)—, —O—,—S—, —NR′— or —C(O)OC(O)—. In certain embodiments X is —NH—, —S— or —O—.In certain embodiments X is —O—. Optionally X is a bond.

M is an alkyl or

In certain embodiment M is alkyl. In certain other embodiments M is aC1-C20 linear or branched chain alkyl. In certain other embodiments M isa C5-C20 linear or branched chain alkyl. In certain other embodiments Mis decane. Additionally M is —H;

each M′ is independently —H, alkyl, or

In certain embodiments, each M′ is independently —H or alkyl;

each n is independently a positive integer from 1 to 6. In certainembodiments, each n is independently integers from 1 to 4.

each m is independently 0 or a positive integer from 1 to 6. In certainembodiments, each m is independently integers from 0 to 4;

each q is independently an integer from 0 to 3. In certain embodiments qis 0;

k in each occurrence independently is a positive integer from 1 to 12;

l in each occurrence, independently is 0 or a positive integer from 1 to12; and

each s, q and u are independently integers from 0 to 4. In certainembodiments, each s and q are independently integers from 0 to 2. Inother embodiments, s is 2. In certain embodiments, each s, and u areindependently integers from 0 to 4; and r is an integer from 0 to 4. Inother embodiments each s, q and r are independently integers from 0 to2.

In a first embodiment for compounds of Structural formula III:

A is —C(O)O—, —OC(O)—, —C(O)NH—, —NHC(O)—, —NH—, —O— or —C(O)—;

R′ is —H;

each R** is independently an optionally substituted alkyl or optionallysubstituted alkoxycarbonyl;

each R₂ is independently an optionally substituted alkyl;

X is —O—;

M is —H or an alkyl;

each n is independently integers from 1 to 4;

each m is independently integers from 0 to 4; and

each s and q are independently integers from 0 to 2 and the remainder ofthe variables are as described above.

In a second embodiment for compounds of Structural formula III:

A is —C(O)NH— or —NHC(O)—;

each R** is independently an alkyl or an alkoxycarbonyl;

each R₂ is independently an alkyl; and

s is 2 and the remainder of the variables are as described above in thefirst embodiment.

In a third embodiment for compounds of Structural formula III:

each R** is independently an alkyl group and the remainder of thevariables are as described above in the second embodiment.

In a fourth embodiment for compounds of Structural formula III:

each R** is independently a tert-butyl group and the remainder of thevariables are as described above in the third embodiment.

In a fifth embodiment for compounds of Structural formula III:

both R** are ortho to the —OH group and the remainder of the variablesare as described above in the fourth embodiment.

In a first embodiment for compounds of Structural formula IV:

A is —C(O)O—, —OC(O)—, —C(O)NH—, —NHC(O)—, —NH—, —O— or —C(O)—;

R′ is —H;

each R** is independently an optionally substituted alkyl or optionallysubstituted alkoxycarbonyl;

each R₂ is independently an optionally substituted alkyl.

each M′ is independently —H or alkyl;

X is —O—;

each n is independently a positive integers from 1 to 4;

each m is independently 0 or a positive integer from 0 to 2; and

each s, q and r are independently integers from 0 to 2 and the remainderof the variables are as described above.

In a second embodiment for compounds of Structural formula IV:

A is —C(O)NH— or —NHC(O)—;

each R** is independently an alkyl or an alkoxycarbonyl; and

s is 2 and the remainder of the variables are as described above in thefirst embodiment.

In a third embodiment for compounds of Structural formula IV:

each R** is independently an alkyl group and the remainder of thevariables are as described above in the second embodiment.

In a fourth embodiment for compounds of Structural formula IV:

each R** is independently a tert-butyl group and the remainder of thevariables are as described above in the third embodiment.

In a fifth embodiment for compounds of Structural formula IV:

both R** are ortho to the —OH group and the remainder of the variablesare as described above in the fourth embodiment.

In a third embodiment for compounds of Structural formula IV:

The term “alkyl” as used herein means a saturated straight-chain,branched or cyclic hydrocarbon. When straight-chained or branched, analkyl group is typically C1-C20, more typically C1-C10; when cyclic, analkyl group is typically C3-C12, more typically C3-C7. Examples of alkylgroups include methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyland tert-butyl and 1,1-dimethylhexyl.

An “aliphatic group” is non-aromatic, consists solely of carbon andhydrogen and may optionally contain one or more units of unsaturation,e.g., double and/or triple bonds. An aliphatic group may bestraight-chained or branched and typically contains between 1 and 12carbon atoms, more typically between 1 and 6 carbon atoms, and even moretypically between 1 and 4 carbon atoms. An aliphatic group may beoptionally substituted at any “substitutable carbon atom”. A“substitutable carbon atom” in an aliphatic group is a carbon in thealiphatic group that is bonded to one or more hydrogen atoms. One ormore hydrogen atoms can be optionally replaced with a suitablesubstituent group. A bivalent aliphatic group is a bivalent grouprepresented by -aliphatic-, wherein aliphatic is an aliphatic group asdefined above.

An “alkylene group” is represented by —[CH₂]_(z)—, wherein z is apositive integer, preferably from one to eight, more preferably from oneto six, wherein optionally one or more hydrogen atoms are optionallyreplaced with suitable substituents. Suitable substituents for analkylene group are as defined below for aliphatic groups. Preferredsubstituents include alkyl, hydroxyl, alkoxy, amine, alkylamine,dialkylamine, oxo, halo, hydroxyalkyl, alkoxyalkyl and aminoalkyl.

The term “alkoxy” as used herein is represented by —OR**, wherein R** isan alkyl group as defined above.

The term “carbonyl” as used herein is represented by —C(═O)R**, whereinR** is an alkyl group as defined above.

The term “alkoxycarbonyl” as used herein is represented by —C(═O)OR**,wherein R** is an alkyl group as defined above.

The term “aromatic group” includes carbocyclic aromatic rings andheteroaryl rings. The term “aromatic group” may be used interchangeablywith the terms “aryl”, “aryl ring” “aromatic ring”, “aryl group” and“aromatic group”.

Carbocyclic aromatic ring groups have only carbon ring atoms (typicallysix to fourteen) and include monocyclic aromatic rings such as phenyland fused polycyclic aromatic ring systems in which a carbocyclicaromatic ring is fused to one or more aromatic rings (carbocyclicaromatic or heteroaromatic). Examples include 1-naphthyl, 2-naphthyl,1-anthracyl and 2-anthracyl. Also included within the scope of the term“carbocyclic aromatic ring”, as it is used herein, is a group in whichan aromatic ring is fused to one or more non-aromatic rings (carbocyclicor heterocyclic), such as in an indanyl, phthalimidyl, naphthimidyl,phenanthridinyl, or tetrahydronaphthyl.

The term “heteroaryl”, “heteroaromatic”, “heteroaryl ring”, “heteroarylgroup” and “heteroaromatic group”, used alone or as part of a largermoiety as in “heteroaralkyl” refers to heteroaromatic ring groups havingfive to fourteen members, including monocyclic heteroaromatic rings andpolycyclic aromatic rings in which a monocyclic aromatic ring is fusedto one or more other aromatic ring (carbocyclic or heterocyclic).Heteroaryl groups have one or more ring heteroatoms. Examples ofheteroaryl groups include 2-furanyl, 3-furanyl, N-imidazolyl,2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-isoxazolyl, 4-isoxazolyl,5-isoxazolyl, oxadiazolyl, oxadiazolyl, 2-oxazolyl, 4-oxazolyl,5-oxazolyl, N-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl,N-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl,2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl,4-pyridazinyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, triazolyl,tetrazolyl, 2-thienyl, 3-thienyl, carbazolyl, benzothienyl,benzofuranyl, indolyl, quinolinyl, benzothiazole, benzooxazole,benzimidazolyl, isoquinolinyl and isoindolyl. Also included within thescope of the term “heteroaryl”, as it is used herein, is a group inwhich an aromatic ring is fused to one or more non-aromatic rings(carbocyclic or heterocyclic).

The term non-aromatic heterocyclic group used alone or as part of alarger moiety refers to non-aromatic heterocyclic ring groups havingthree to fourteen members, including monocyclic heterocyclic rings andpolycyclic rings in which a monocyclic ring is fused to one or moreother non-aromatic carbocyclic or heterocyclic ring or aromatic ring(carbocyclic or heterocyclic). Heterocyclic groups have one or more ringheteroatoms, and can be saturated or contain one or more units ofunsaturation. Examples of heterocyclic groups include piperidinyl,piperizinyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl,tetrahydroquinolinyl, inodolinyl, isoindolinyl, tetrahydrofuranyl,oxazolidinyl, thiazolidinyl, dioxolanyl, dithiolanyl, tetrahydropyranyl,dihydropyranyl, azepanyl and azetidinyl

The term “heteroatom” means nitrogen, oxygen, or sulfur and includes anyoxidized form of nitrogen and sulfur, and the quaternized form of anybasic nitrogen. Also the term “nitrogen” includes a substitutablenitrogen of a heteroaryl or non-aromatic heterocyclic group. As anexample, in a saturated or partially unsaturated ring having 0-3heteroatoms selected from oxygen, sulfur or nitrogen, the nitrogen maybe N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl) or NR″ (asin N-substituted pyrrolidinyl), wherein R″ is a suitable substituent forthe nitrogen atom in the ring of a non-aromatic nitrogen-containingheterocyclic group, as defined below. Preferably the nitrogen isunsubstituted.

As used herein the term non-aromatic carbocyclic ring as used alone oras part of a larger moiety refers to a non-aromatic carbon containingring which can be saturated or contain one or more units ofunsaturation, having three to fourteen atoms including monocyclic andpolycyclic rings in which the carbocyclic ring can be fused to one ormore non-aromatic carbocyclic or heterocyclic rings or one or morearomatic (carbocyclic or heterocyclic) rings

An optionally substituted aryl group as defined herein may contain oneor more substitutable ring atoms, such as carbon or nitrogen ring atoms.Examples of suitable substituents on a substitutable ring carbon atom ofan aryl or aliphatic group include halogen (e.g., —Br, Cl, I and F),—OH, C1-C4 alkyl, C1-C4 haloalkyl, —NO₂, C1-C4 alkoxy, C1-C4 haloalkoxy,—CN, —NH₂, C1-C4 alkylamino, C1-C4 dialkylamino, —C(O)NH₂, —C(O)NH(C1-C4alkyl), —C(O)(C1-C4 alkyl), —OC(O)(C1-C4 alkyl), —OC(O)(aryl),—OC(O)(substituted aryl), —OC(O)(aralkyl), —OC(O)(substituted aralkyl),—NHC(O)H, —NHC(O)(C1-C4 alkyl), —C(O)N(C1-C4 alkyl)₂, —NHC(O)O—(C1-C4alkyl), —C(O)OH, —C(O)O—(C1-C4 alkyl), —NHC(O)NH₂, —NHC(O)NH(C1-C4alkyl), —NHC(O)N(C1-C4 alkyl)₂, —NH—C(═NH)NH₂,—SO₂NH₂—SO₂NH(C1-C3alkyl), —SO₂N(C1-C3alkyl)₂, NHSO₂H, NHSO₂(C1-C4alkyl) and aryl. Preferred substituents on aryl groups are as definedthroughout the specification. In certain embodiments aryl groups areunsubstituted.

Examples of suitable substituents on a substitutable ring nitrogen atomof an aryl group include C1-C4 alkyl, NH₂, C1-C4 alkylamino, C1-C4dialkylamino, —C(O)NH₂, —C(O)NH(C1-C4 alkyl), —C(O)(C1-C4 alkyl),—CO₂R**, —C(O)C(O)R**, —C(O)CH₃, —C(O)OH, —C(O)O—(C1-C4 alkyl),—SO₂NH₂—SO₂NH(C1-C3alkyl), —SO₂N(C1-C3alkyl)₂, NHSO₂H, NHSO₂(C1-C4alkyl), —C(═S)NH₂, —C(═S)NH(C1-C4 alkyl), —C(═S)N(C1-C4 alkyl)₂,—C(═NH)—N(H)₂, —C(═NH)—NH(C1-C4 alkyl) and —C(═NH)—N(C1-C4 alkyl)₂,

An optionally substituted alkyl group, alkylene, or aliphaitc ornon-aromatic carbocyclic or heterocyclic group as defined herein maycontain one or more substituents. Examples of suitable substituents foran alkyl group include those listed above for a substitutable carbon ofan aryl and aliphatic and the following: ═O, ═S, ═NNHR**, ═NN(R**)₂,═NNHC(O)R**, ═NNHCO₂ (alkyl), ═NNHSO₂ (alkyl), ═NR**, spiro cycloalkylgroup or fused cycloalkyl group. R** in each occurrence, independentlyis —H or C1-C6 alkyl. Preferred substituents on alkyl groups are asdefined throughout the specification. In certain embodiments optionallysubstituted alkyl groups are unsubstituted.

A “spiro cycloalkyl” group is a cycloalkyl group which shares one ringcarbon atom with a carbon atom in an alkylene group or alkyl group,wherein the carbon atom being shared in the alkyl group is not aterminal carbon atom.

As used herein, the terms “a bond” and “absent” to described possiblevalues for the variables described herein can be used interchangeably.

In yet another embodiment, the present invention is a method ofproducing a compound described herein using methods know in the art oforganic chemistry.

In certain embodiments this invention can allow synthesizingmacromolecular antioxidants cost effectively. In these embodiments thesemethods also reports an improved, highly efficient and economicalprocess for the synthesis of macromolecular antioxidants.

As used herein an “antioxidant moiety” is a molecule or a portion of amolecule which has itself antioxidant properties, for example a phenolicgroup. A molecule which has two phenolic groups has, for example, twoantioxidant moieties, i.e, each phenolic group which is capable ofacting as a proton donor is an antioxidant moiety.

The present invention relates to macromolecular compounds possessingantioxidant properties comprising more than one type of antioxidantmoieties (for example, W1H and W2H), and methods of inhibiting oxidationin a substance comprising contacting the substance with the antioxidantsdescribed herein. This is achieved by coupling these unique structuralunits to di-, tri- and tetra- functional molecules providing a singlemacromolecule with multiple antioxidant moieties acting synergisticallyamong themselves. The conceptual designs of these possiblemacromolecular antioxidants are shown here for the active parts of themolecule. The reaction activities of these antioxidant moieties areselected so that transfer equilibrium among the moieties is maintainedso that regeneration of moieties is possible proving enhanced oxidationinhibition. This is illustrated below.

Consider a multifunctional antioxidant containing two different kinds ofactive moieties or (W1H and W2H), each of which is capable of acting asa hydrogen atom donor to a peroxy radical. With this multifunctionalantioxidant there are two possible inhibition reactions (1a) and (1b):

R—OO.+W1H→R—OOH+W1.  (1a)

R—OO.+W2H→R—OOH+W2.  (1b)

The antioxidant is designed in such a way that the moiety W1H is muchmore reactive than the W2H i.e. k_(1a)>k_(1b). In model oxidationstudies conducted with antioxidants having similar warheads, the ratiok_(1a)/k_(1b) is ˜20.

The radicals derived from W1H and W2H present different levels ofreactivity in propagation reaction (2). Once again, there are twopossible propagation reactions (2a) and (2b):

R—H+W1.→R.+W1H  (2a)

R—H+W2.→R.+W2H  (2b)

In this multifunctional antioxidant, W1. is much more reactive than W2.,i.e. k_(2a)>>k_(2b). In model studies conducted using antioxidants withsimilar warheads, only reaction (2a) could be observed.

The undesired propagation reaction (2a) is effectively prevented by atransfer equilibrium reaction (3), which regenerates the highly activeantioxidant warhead W1H and gives the stable radical W2. as aby-product:

W1.+W2H

W1H+W2.  (3)

The commercial antioxidants are normally sacrificial. It means thatthese molecules become inactive after they participated in the oxidationinhibiting event. On the contrary, the design of new antioxidantssuggests (equation 3) that some of these antioxidant activities areregenerated through W1H while others are sacrificed (W2H) at the sametime. The net result is that novel antioxidants provide extendedprotection.

In various embodiments, the macromolecular antioxidants of the presentinvention can be prepared as shown below:

In certain embodiments the present invention is a method of synthesizinga macromonomer represented by the following structural formula:

wherein:

R is:

A in each occurrence, independently is —O—, —NH—, —S—, —C(O)—, —C(O)NH—,—NHC(O)—, —C(O)O—, —OC(O)—, —CH═N— or —N═CH—;

A′ in each occurrence, independently is a bond, —O—, —NH—, —S—, —C(O)—,—C(O)NH—, —NHC(O)—, —C(O)O—, —OC(O)—, —CH═N— or —N═CH—;

B in each occurrence, independently is a bond or an optionallysubstituted alkylene group;

C in each occurrence independently is —H, an optionally substitutedalkylene group or

R₁ and R₂ in each occurrence, independently is an optionally substitutedalkyl, optionally substituted aryl or optionally substituted aralkyl;

Z in each occurrence, independently is a bond, an optionally substitutedalkylene group, —(CH₂)₁NHC(O)(CH₂)₁—, —(CH₂)₁C(O)NH(CH₂)₁—,—(CH₂)₁C(O)O(CH₂)₁—, —(CH₂)₁OC(O)(CH₂)₁—, —(CH₂)₁CH═N(CH₂)₁—,—(CH₂)₁N═CH(CH₂)₁—, —(CH₂)₁NH(CH₂)₁—, —(CH₂)₁S(CH₂)₁—, —(CH₂)₁O(CH₂)₁—or —(CH₂)₁C(O)(CH₂)₁—;

i in each occurrence, independently is 0, 1, 2 or 3;

j in each occurrence, independently is 0, 1, 2, 3 or 4;

l in each occurrence, independently is 0 or a positive integer from 1 to12; comprising the step of combining R⁺⁺, wherein R⁺⁺ is:

with X, wherein X is represented by the following structural formula:

D in each occurrence, independently is halogen, haloalkyl,—(CH₂)₁—NHC(O)—F, —(CH₂)₁—C(O)NH—F, —(CH₂)₁—C(O)O—F, —(CH₂)₁—OC(O)—F,—(CH₂)₁—CH═N—F, —(CH₂)₁—N═CH—F, —(CH₂)₁—NH—F, —(CH₂)₁—S—F, —(CH₂)₁O—F or—(CH₂)₁—C(O)—F; and

F in each occurrence, independently is —H, halogen, haloalkyl or analiphatic group.

In certain embodiments: D in each occurrence, independently is—(CH₂)₁—C(O)O—F, —(CH₂)₁—OC(O)—F, —(CH₂)₁O—F or —(CH₂)₁—C(O)—F;

F in each occurrence, independently is —H, halogen, or a C1-C3 alkenylgroup; and

l in each occurrence, independently is 0 or a positive integer from 1 to6.

In certain other embodiments, D in each occurrence, independently is—(CH₂)₁O—F, —(CH₂)₁—C(O)O—F or —(CH₂)₁—OC(O)—F;

F in each occurrence, independently is —H or a C1-C3 alkenyl group; and

l in each occurrence, independently is 0 or a positive integer from 1 to3.

In certain other embodiments X is:

In certain other embodiments, R⁺⁺ is:

wherein:

n is an integer from 0 to 4;

i is 0 or 1; and

R₁ is a C1-C6 alkyl.

In certain other embodiments, the macromonomer is represented by thefollowing structural formula:

In certain embodiments the present invention is a method of synthesizinga macromonomer represented by the following structural formula:

wherein:

R is:

A in each occurrence, independently is —O—, —NH—, —S—, —C(O)—, —C(O)NH—,—NHC(O)—, —C(O)O—, —OC(O)—, —CH═N— or —N═CH—;

A′ in each occurrence, independently is a bond, —O—, —NH—, —S—, —C(O)—,—C(O)NH—, —NHC(O)—, —C(O)O—, —OC(O)—, —CH═N— or —N═CH—;

B in each occurrence, independently is a bond or an optionallysubstituted alkylene group;

C in each occurrence independently is —H, an optionally substitutedalkylene group or

R₁ and R₂ in each occurrence, independently is an optionally substitutedalkyl, optionally substituted aryl or optionally substituted aralkyl;

Z in each occurrence, independently is a bond, an optionally substitutedalkylene group, —(CH₂)₁NHC(O)(CH₂)₁—, —(CH₂)₁C(O)NH(CH₂)₁—,—(CH₂)₁C(O)O(CH₂)₁—, —(CH₂)₁OC(O)(CH₂)₁—, —(CH₂)₁CH═N(CH₂)₁—,—(CH₂)₁N═CH(CH₂)₁—, —(CH₂)₁NH(CH₂)₁—, —(CH₂)₁S(CH₂)₁—, —(CH₂)₁O(CH₂)₁—or —(CH₂)₁C(O)(CH₂)₁—;

i in each occurrence, independently is 0, 1, 2 or 3;

j in each occurrence, independently is 0, 1, 2, 3 or 4;

l in each occurrence, independently is 0 or a positive integer from 1 to12; and comprising the step of combining R⁺⁺⁺, wherein R⁺⁺⁺ is:

with X′, wherein X′ is represented by the following structural formula:

Q is —OH, NH₂ or SH;

D is halogen, haloalkyl, —(CH₂)₁—NHC(O)—F, —(CH₂)₁—C(O)NH—F,—(CH₂)₁—C(O)O—F, —(CH₂)₁—OC(O)—F, —(CH₂)₁—CH═N—F, —(CH₂)₁—N═CH—F,—(CH₂)₁—NH—F, —(CH₂)₁—S—F, —(CH₂)₁O—F or —(CH₂)₁—C(O)—F; and

F in each occurrence, independently is —H, halogen, haloalkyl or analiphatic group.

In certain embodiments, D is —(CH₂)₁—C(O)O—F, —(CH₂)₁—OC(O)—F,—(CH₂)₁₀—F or —(CH₂)₁—C(O)—F;

F is —H or halogen; and

l in each occurrence, independently is 0 or a positive integer from 1 to6.

In certain other embodiments, D is —(CH₂)₁—C(O)O—F or —(CH₂)₁—OC(O)—F;and

F is —H; and

l in each occurrence, independently is 0 or a positive integer from 1 to3.

In certain other embodiments, X′ is:

In certain other embodiments, R⁺⁺⁺ is:

wherein:

n is an integer from 0 to 4;

l is i an integer from 0 to 2;

i is 0 or 1; and

R₁ is C1-C6 alkyl.

In certain other embodiments, the macromonomer is represented by thefollowing structural formula:

In certain embodiments the present invention is a method of synthesizinga macromonomer represented by the following structural formula:

wherein:

R is:

A in each occurrence, independently is —O—, —NH—, —S—, —C(O)—, —C(O)NH—,—NHC(O)—, —C(O)O—, —OC(O)—, —CH═N— or —N═CH—;

A′ in each occurrence, independently is a bond, —O—, —NH—, —S—, —C(O)—,—C(O)NH—, —NHC(O)—, —C(O)O—, —OC(O)—, —CH═N— or —N═CH—;

B in each occurrence, independently is a bond or an optionallysubstituted alkylene group;

C in each occurrence independently is —H, an optionally substitutedalkylene group or

R₁ and R₂ in each occurrence, independently is an optionally substitutedalkyl, optionally substituted aryl or optionally substituted aralkyl;

Z in each occurrence, independently is a bond, an optionally substitutedalkylene group, —(CH₂)₁NHC(O)(CH₂)₁—, —(CH₂)₁C(O)NH(CH₂)₁—,—(CH₂)₁C(O)O(CH₂)₁—, —(CH₂)₁OC(O)(CH₂)₁—, —(CH₂)₁CH═N(CH₂)₁—,—(CH₂)₁N═CH(CH₂)₁—, —(CH₂)₁NH(CH₂)₁—, —(CH₂)₁S(CH₂)₁—, —(CH₂)₁O(CH₂)₁—or —(CH₂)₁C(O)(CH₂)₁—;

i in each occurrence, independently is 0, 1, 2 or 3;

j in each occurrence, independently is 0, 1, 2, 3 or 4;

l in each occurrence, independently is 0 or a positive integer from 1 to12;

s is a positive integer from 1 to 6;

comprising the step of combining R′″, wherein R′″ is:

with X″, wherein X″ is represented by the following structural formula:

and

D is halogen, haloalkyl, —(CH₂)₁—NHC(O)—F, —(CH₂)₁—C(O)NH—F,—(CH₂)₁—C(O)O—F, —(CH₂)₁—OC(O)—F, —(CH₂)₁—CH═N—F, —(CH₂)₁—N═CH—F,—(CH₂)₁—NH—F, —(CH₂)₁—S—F, —(CH₂)₁O—F or —(CH₂)₁—C(O)—F; and

D′ is —(CH₂)₁—C(O)O—F, —(CH₂)₁—OC(O)—F or —(CH₂)₁O—F′; and

F in each occurrence, independently is —H, halogen, haloalkyl or analiphatic group; and

F′ in each occurrence, independently is —H, halogen, haloalkyl or analiphatic group.

In certain embodiments,

D is —(CH₂)₁—C(O)O—F, —(CH₂)₁—OC(O)—F, —(CH₂)₁₀—F or —(CH₂)₁—C(O)—F;

F in each occurrence, independently is —H, halogen, or a C1-C3 alkenylgroup; and

l in each occurrence, independently is 0 or a positive integer from 1 to6;

In certain other embodiments,

D′ is —(CH₂)₁O—F;

D is —(CH₂)₁—C(O)—F;

F is halogen;

F′ is —H; and

l in each occurrence, independently is 0 or a positive integer from 1 to3.

In certain other embodiments, X″ is:

In certain other embodiments, R⁺⁺⁺ is:

wherein

n is an integer from 0 to 2;

l is i an integer from 0 to 2;

i is 0 or 1; and

R₁ is —H or optionally substituted alkyl.

In certain other embodiments, the macromonomer is represented by thefollowing structural formula:

In certain embodiments the present invention is a method of synthesizinga macromonomer represented by the following structural formula:

wherein:

R is:

A in each occurrence, independently is —O—, —NH—, —S—, —C(O)—, —C(O)NH—,—NHC(O)—, —C(O)O—, —OC(O)—, —CH═N— or —N═CH—;

A′ in each occurrence, independently is a bond, —O—, —NH—, —S—, —C(O)—,—C(O)NH—, —NHC(O)—, —C(O)O—, —OC(O)—, —CH═N— or —N═CH—;

B in each occurrence, independently is a bond or an optionallysubstituted alkylene group;

C in each occurrence independently is —H, an optionally substitutedalkylene group or

R₁ and R₂ in each occurrence, independently is an optionally substitutedalkyl, optionally substituted aryl or optionally substituted aralkyl;

Z in each occurrence, independently is a bond, an optionally substitutedalkylene group, —(CH₂)₁NHC(O)(CH₂)₁—, —(CH₂)₁C(O)NH(CH₂)₁—,—(CH₂)₁C(O)O(CH₂)₁—, —(CH₂)₁OC(O)(CH₂)₁—, —(CH₂)₁CH═N(CH₂)₁—,—(CH₂)₁N═CH(CH₂)₁—, —(CH₂)₁NH(CH₂)₁—, —(CH₂)₁S(CH₂)₁—, —(CH₂)₁O(CH₂)₁—or —(CH₂)₁C(O)(CH₂)₁—;

i in each occurrence, independently is 0, 1, 2 or 3;

j in each occurrence, independently is 0, 1, 2, 3 or 4;

l in each occurrence, independently is 0 or a positive integer from 1 to12;

s is a positive integer from 1 to 6;

comprising the step of combining R*, wherein R* is:

with X′″, wherein X′″ is represented by the following structuralformula:

and

A″ is NO₂, NH₂ or OH;

Q is —OH;

D is halogen, haloalkyl, —(CH₂)₁—NHC(O)—F, —(CH₂)₁—C(O)NH—F,—(CH₂)₁—C(O)O—F, —(CH₂)₁—OC(O)—F, —(CH₂)₁—CH═N—F, —(CH₂)₁—N═CH—F,—(CH₂)₁—NH—F, —(CH₂)₁—S—F, —(CH₂)₁₀—F or —(CH₂)₁—C(O)—F; and

F in each occurrence, independently is —H, halogen, haloalkyl or analiphatic group;

to produce Y, wherein Y is represented by the following structuralformula:

wherein:

Q′ is —O—;

D″ is a bond, alkylene, —(CH₂)₁—NHC(O)—F″, —(CH₂)₁—C(O)NH—F″,—(CH₂)₁—C(O)O—F″, —(CH₂)₁—OC(O)—F″, —(CH₂)₁—CH═N—F″, —(CH₂)₁—N═CH—F″,—(CH₂)₁—NH—F″, —(CH₂)₁—S—F, —(CH₂)₁₀—F″ or —(CH₂)₁—C(O)—F″; and

F″ in each occurrence, independently is absent or bivalent aliphaticgroup.

In certain embodiments, D is halogen or haloalkyl.

In certain other embodiments, X′″ is:

In certain other embodiments, R* is:

In certain other embodiments, the method further comprises the step ofcombining Y with U, wherein U is represented by the following structuralformula:

wherein:

G is —COOH or COOalkyl

to produce the macromonomer.

In certain embodiments, U is:

In certain other embodiments, the macromonomer is represented by thefollowing structural formula:

The compounds in Scheme I in general are synthesized by dissolving aphenol in THF in the presence of a base (such as potassium-t-butoxide)and reacting the resultant carbanions with an acrylate under Michael'saddition reaction conditions. N-methyl pyrollodine, dichlorobenzene anddimethoxy benzene are the other solvents that can used in the reaction.The reaction can also be done using sodium or potassium methoxide,lithium diisopropylamide (LDA)

The compound shown in Scheme II in general are synthesized by reacting aphenol with formaldehyde in a suitable solvent in the presence of acidicor basic catalyst at a temperature 40° C.-130° C. The solvents which aresuitable in this reaction includes methanol, ethanol, toluene.

The compounds shown in Scheme 3 in general can be synthesized by adding,combining, suspending or dissolving equimolar amounts of acid and DCC inTHF and optionally stirring. Suitable stirring times include less than 5hours, less than 3 hours, less than 1 hour. To this optionally stirredsolution in general pentaerythritol and catalytic amounts of DMAP areadded. The reaction mixture can optionally be stirred for less than 48hours, less than 36 hours, less than 24 hours to get the desiredproduct.

In general compound shown in Scheme 4 are synthesized by adding,suspending or dissolving, for example, lithium aluminium hydride inanhydrous THF under, for example, a nitrogen atmosphere at 0° C. Theresultant solution/suspension can optionally be stirred. To thisoptionally stirred solution/suspension, for example, phenol methyl esteris added drop-wise while maintaining the temperature at between 50 and−50° C. between 25 and −25° C. between 5 and −5° C., between 1 and −1°C., between 0.5 and −0.5° C., or at 0° C. After complete addition, thereaction mixture can optionally be allowed to warm to room temperatureand optionally stirred for less than 5 hours, less than 3 hours, lessthan 2 hours. After completion, the reaction can optionally be quenchedby adding a mixture of, for example, methanol and water and the productalcohol can be was isolated by extraction with, for example, ethylacetate. The alcohol is optionally dried.

In the second step, the alcohol can be dissolved in anhydrous THFfollowed by the addition of 1,3,5-benzene tri acyl chloride in thepresence of triethyl amine.

The compound shown in scheme 5 can be prepared in three steps startingwith, for example, trihydroxy benzene (phloroglucinol). Phloroglucinolcan be alkylated with, for example, 5-nitro, 2-phenol benzyl bromide bydissolving in acetone in the presence of potassium carbonate. In thenext step the alkkylated nitrophenol can be reduced to alkylated phenolamine using tin and hydrochloric acid. The Alkylated phenol amine can becondensed with, for example, 3-(2,6-di-tert-butylphenol) propanoic acidto obtain the desired compound.

In various embodiments, the compounds of the present invention can beprepared as shown in the following Scheme:

In certain embodiments the present invention is a method of making thecompounds of the present invention comprising the steps of dissolving orsuspending the starting material in a suitable solvent, such as,methanol or ethanol; adding a suitable reagent, such as, an aldehyde,for example, paraformaldehyde under suitable acidic conditions, such as,for example in the presence of hydrochloric acid. The mixture of thestarting material, solvent acid and reagent can then be refluxed atbetween 0 and 100° C., between 10 and 90° C., between 20 and 80° C.,between 40 and 70° C. or between 60 and 70° C. The progress of thereaction can be monitored by thin-layer chromatography. After completionof the reaction the solvent can be removed by distillation under vacuum.The remaining solid can then be washed with water and dried to obtainthe polymer.

In various embodiments, the compounds of the present invention can beprepared as shown in the following Scheme:

In various embodiments, the compounds of the present invention can beprepared as shown in the following Scheme:

In certain embodiments the present invention is a method of making acompound represented by the following Structural Formula:

wherein:

A is —C(O)NR′—, —NR′C(O)—, —NR′—, —CR′═N—, —C(O)—, —C(O)O—, —OC(O)—,—O—, —S—, —C(O)OC(O)— or a bond;

each R′ is independently —H or optionally substituted alkyl;

each R** is independently an optionally substituted alkyl, optionallysubstituted aryl, optionally substituted alkoxycarbonyl, optionallysubstituted ester, —OH, —NH₂, —SH, or

each R₁ and R₂ is independently an optionally substituted alkyl,optionally substituted aryl, optionally substituted alkoxycarbonyl,optionally substituted ester, —OH, —NH₂ or —SH;

X is —C(O)O—, —OC(O)—, —C(O)NR′—, —NR′C(O)—, —NR′—, —CH═N—, —C(O)—, —O—,—S—, —NR′— or —C(O)OC(O)—;

M is —H, an alkyl or

each n is independently a positive integer from 1 to 6;

each m is independently 0 or a positive integer from 1 to 6; and

each s, q and u are independently integers from 0 to 4;

comprising the steps of combining G, wherein G is represented by thefollowing structural formula:

wherein g is a phenolic acid with H, wherein H is represented by thefollowing structural formula:

In another embodiment the present invention is a method of making acompound represented by the following Structural Formula:

R—Z—(CH₂)_(k)—Z—R

wherein R is:

A is —C(O)NR′—, —NR′C(O)—, —NR′—, —CR′═N—, —C(O)—, —C(O)O—, —OC(O)—,—O—, —S—, —C(O)OC(O)— or a bond;

Z in each occurrence, independently is a bond, an optionally substitutedalkylene group, —(CH₂)₁NHC(O)(CH₂)₁—, —(CH₂)₁C(O)NH(CH₂)₁—,—(CH₂)₁C(O)O(CH₂)₁—, —(CH₂)₁OC(O)(CH₂)₁—, —(CH₂)₁CH═N(CH₂)₁—,—(CH₂)₁N═CH(CH₂)₁—, —(CH₂)₁NH(CH₂)₁—, —(CH₂)₁S(CH₂)₁—, —(CH₂)₁O(CH₂)₁—or —(CH₂)₁C(O)(CH₂)₁—;

each R′ is independently —H or optionally substituted alkyl;

each R** is independently an optionally substituted alkyl, optionallysubstituted aryl, optionally substituted alkoxycarbonyl, optionallysubstituted ester, —OH, —NH₂, —SH, or

each R₁ and R₂ is independently an optionally substituted alkyl,optionally substituted aryl, optionally substituted alkoxycarbonyl,optionally substituted ester, —OH, —NH₂ or —SH;

X is —C(O)O—, —OC(O)—, —C(O)NR′—, —NR′C(O)—, —NR′—, —CR′═N—, —C(O)—,—O—, —S—, —NR′— or —C(O)OC(O)—;

each M′ is independently —H, alkyl, or

each n is independently a positive integer from 1 to 6;

each m is independently 0 or a positive integer from 1 to 6;

l in each occurrence, independently is 0 or a positive integer from 1 to12; and

k in each occurrence independently is a positive integer from 1 to 12;

each q is independently an integer from 0 to 3;

each s, and u are independently integers from 0 to 4; and

r is an integer from 0 to 4;

comprising the steps of polymerizing a compound represented by thefollowing structural formula:

and isolating the polymer.

In certain embodiments these macromolecular antioxidants can havesignificantly higher antioxidant activities along with improved thermalstability and performance in a wide range of materials including but notlimited to plastics, elastomers, lubricants, petroleum based products(lubricants, gasoline, aviation fuels, and engine oils), cooking oil,cosmetics, processed food products, compared to commercially availableantioxidants. In certain embodiments the present invention alsodiscloses the superior performance of macromolecules of the formula I inmaterials including but not limited to polyolefins.

The compounds of the present invention can be used as antioxidants toinhibit oxidation of an oxidizable material. Such as, for example toincrease the shelf life of an oxidizable material.

The antioxidant compounds of the present invention can be employed toinhibit the oxidation of an oxidizable material, for example bycontacting the material with an antioxidant compound of the presentinvention.

For purposes of the present invention, a method of “inhibitingoxidation” is a method that inhibits the propagation of a freeradical-mediated process. Free radicals can be generated by heat, light,ionizing radiation, metal ions and some proteins and enzymes. Inhibitingoxidation also includes inhibiting reactions caused by the presence ofoxygen, ozone or another compound capable of generating these gases orreactive equivalents of these gases.

As used herein the term “oxidizable material” is any material which issubject to oxidation by free-radicals or oxidative reaction caused bythe presence of oxygen, ozone or another compound capable of generatingthese gases or reactive equivalents thereof.

In certain embodiments, the oxidizable material is an organic polymer orplastic. In certain embodiments, the oxidizable material is anelastomer. In certain embodiments, the oxidizable material is alubricant. In certain embodiments, the oxidizable material is apetroleum based product. In certain embodiments, the oxidizable materialis an edible oil or cooking oil. In certain embodiments, the oxidizablematerial is a cosmetic. In certain embodiments, the oxidizable materialis a processed food product.

In particular the oxidizable material is a lubricant or a mixture oflubricants.

The shelf life of many materials and substances contained within thematerials, such as packaging materials, are enhanced by the presence ofthe antioxidants of the present invention. The addition of anantioxidant of the present invention to a packaging material is believedto provide additional protection to the product contained inside thepackage. In addition, the properties of many packaging materialsthemselves, particularly polymers, are enhanced by the presence of anantioxidant regardless of the application (i.e., not limited to use inpackaging). Common examples of packaging materials include paper,cardboard and various plastics and polymers. A packaging material can becoated with an antioxidant (e.g., by spraying the antioxidant or byapplying as a thin film coating), blended with or mixed with anantioxidant, or otherwise have an antioxidant present within it. In oneexample, a thermoplastic such as polyethylene, polypropylene orpolystyrene can be melted in the presence of an antioxidant in order tominimize its degradation during the polymer processing.

The lifetime of lubricants, lubricant oils, mixtures thereof andcompositions comprising lubricants and lubricant oils in general can beimproved by contacting the lubricant, lubricant oil, mixtures thereof orcomposition comprising the lubricant or lubricant oil or mixturesthereof with compounds of the present invention, as described herein.

In certain embodiments of the present invention, polyolefins andmixtures of polyolefins can be stabilized by contacting the polyolefinor mixture of polyolefins with a compound of the present invention.These polyolefins and mixtures of polyolefins, include, but are notlimited to substituted polyolefins, polyacrylates, polymethacrylates andcopolymers of polyolefins. The following are examples of some types ofpolyolefins which can be stabilized by the methods of the presentinvention:

1. Polymers of monoolefins and diolefins, for example polypropylene,polyisobutylene, polybut-1-ene, poly-4-methylpent-1-ene, polyisoprene orpolybutadiene, as well as polymers of cycloolefins, for instance ofcyclopentene or norbornene, polyethylene (which optionally can becrosslinked), for example high density polyethylene (HDPE), high densityand high molecular weight polyethylene (HDPE-HMW), high density andultrahigh molecular weight polyethylene (HDPE-UHMW), medium densitypolyethylene (MDPE), low density polyethylene (LDPE), linear low densitypolyethylene (LLDPE), very low density polyethylene (VLDPE) and ultralow density polyethylene (ULDPE).

Polyolefins, i.e. the polymers of monoolefins exemplified in thepreceding paragraph, for example polyethylene and polypropylene, can beprepared by different, and especially by the following, methods:

i) radical polymerization (normally under high pressure and at elevatedtemperature).

ii) catalytic polymerization using a catalyst that normally contains oneor more than one metal of groups IVb, Vb, VIb or VIII of the PeriodicTable. These metals usually have one or more than one ligand, typicallyoxides, halides, alcoholates, esters, ethers, amines, alkyls, alkenylsand/or aryls that may be either p- or s-coordinated. These metalcomplexes may be in the free form or fixed on substrates, typically onactivated magnesium chloride, titanium(III) chloride, alumina or siliconoxide. These catalysts may be soluble or insoluble in the polymerizationmedium. The catalysts can be used by themselves in the polymerization orfurther activators may be used, typically metal alkyls, metal hydrides,metal alkyl halides, metal alkyl oxides or metal alkyloxanes, saidmetals being elements of groups Ia, IIa and/or IIIa of the PeriodicTable. The activators may be modified conveniently with further ester,ether, amine or silyl ether groups. These catalyst systems are usuallytermed Phillips, Standard Oil Indiana, Ziegler (-Natta), TNZ (DuPont),metallocene or single site catalysts (SSC).

2. Mixtures of the polymers mentioned under 1., for example, mixtures ofpolypropylene with polyisobutylene, polypropylene with polyethylene (forexample PP/HDPE, PP/LDPE) and mixtures of different types ofpolyethylene (for example LDPE/HDPE).

3. Copolymers of monoolefins and diolefins with each other or with othervinyl monomers, for example ethylene/propylene copolymers, linear lowdensity polyethylene (LLDPE) and mixtures thereof with low densitypolyethylene (LDPE), propylene/but-1-ene copolymers,propylene/isobutylene copolymers, ethylene/but-1-ene copolymers,ethylene/hexene copolymers, ethylene/methylpentene copolymers,ethylene/heptene copolymers, ethylene/octene copolymers,propylene/butadiene copolymers, isobutylene/isoprene copolymers,ethylene/alkyl acrylate copolymers, ethylene/alkyl methacrylatecopolymers, ethylene/vinyl acetate copolymers and their copolymers withcarbon monoxide or ethylene/acrylic acid copolymers and their salts(ionomers) as well as terpolymers of ethylene with propylene and a dienesuch as hexadiene, dicyclopentadiene or ethylidene-norbornene; andmixtures of such copolymers with one another and with polymers mentionedin 1) above, for example polypropylene/ethylene-propylene copolymers,LDPE/ethylene-vinyl acetate copolymers (EVA), LDPE/ethylene-acrylic acidcopolymers (EAA), LLDPE/EVA, LLDPE/EAA and alternating or randompolyalkylene/carbon monoxide copolymers and mixtures thereof with otherpolymers, for example polyamides.

4. Blends of polymers mentioned under 1. with impact modifiers such asethylene-propylene-diene monomer copolymers (EPDM), copolymers ofethylene with higher alpha-olefins (such as ethylene-octene copolymers),polybutadiene, polyisoprene, styrene-butadiene copolymers, hydrogenatedstyrene-butadiene copolymers, styrene-isoprene copolymers, hydrogenatedstyrene-isoprene copolymers. These blends are commonly referred to inthe industry as TPO's (thermoplastic polyolefins).

In certain particular embodiments polyolefins of the present inventionare for example polypropylene homo- and copolymers and polyethylenehomo- and copolymers. For instance, polypropylene, high densitypolyethylene (HDPE), linear low density polyethylene (LLDPE) andpolypropylene random and impact (heterophasic) copolymers.

In certain embodiments of the present invention, 50% to 20% by weight ofthe antioxidants of the present invention are added to the polyolefin.In certain other embodiments of the present invention, 10% to 5% byweight of the antioxidants of the present invention are added to thepolyolefin. In certain other embodiments of the present invention, 0.1%to 2% by weight of the antioxidants of the present invention are addedto the polyolefin. In certain other embodiments of the presentinvention, 0.001% to 0.5% by weight of the antioxidants of the presentinvention are added to the polyolefin. This percentage varies dependingupon their end application and type of the polyolefin.

In certain embodiments of the present invention the antioxidants of thepresent invention are usually added to the polyolefin with stirring atbetween 0 and 100° C., between 10 and 80° C., between 20-30° C. or atroom temperature.

In certain embodiments the antioxidants of the present invention can bemixed with other antioxidants or additives to produce formulations, suchas those described in Docket No.: 3805.1009-000; Provisional PatentApplication No. 60/742,150, filed Dec. 2, 2005, Title: LubricantComposition, by Kumar, Rajesh, et al., and Docket No.: 3805.1010-000;Provisional Patent Application No. 60/731,325, filed Oct. 27, 2005,Title: Stabilized Polyolefin Composition, by Kumar, Rajesh, et al., theentire contents of each of which are incorporated herein by reference.

In certain embodiments the present invention relates to a method ofpreventing oxidation comprising combining an oxidizable material with acompound described herein.

In certain embodiments, the oxidizable material is an organic polymer orplastic. In certain embodiments, the oxidizable material is anelastomer. In certain embodiments, the oxidizable material is alubricant. In certain embodiments, the oxidizable material is apetroleum based product. In certain embodiments, the oxidizable materialis an edible oil or cooking oil. In certain embodiments, the oxidizablematerial is a cosmetic. In certain embodiments, the oxidizable materialis a processed food product.

EXEMPLIFICATION Example 1 Synthesis of Tyramine based AO

11.7 g of butylated hydroxytoluene (BHT) propanoic acid and 0.3 g ofboric acid was dissolved in 50 ml of toluene and refluxed using a DienStark's apparatus for 30 minutes. To this solution was added 5.0 g oftyramine and the resulting solution was refluxed at 130° C. The waterformed during the reaction was removed using Dien Stark's apparatus. Thereaction was monitored by thin layer chromatography. After completion ofthe reaction, toluene was removed by distillation under reduced pressureand the solid obtained was re-dissolved in methanol. The solution inmethanol was added drop wise to acidic water to remove any unreactedamine component. The precipitated solid was filtered and re-dissolved inmethanol and added to basic water to remove any unreacted acidiccomponent. The solid obtained was filtered, dried and analyzed by itsspectral analysis, as shown in FIG. 1-3.

Example 2

The resultant compound wherein n is O and R₁ is Me was synthesized bydissolving the phenol in THF in the presence of potassium-t-butoxide andreacting the resultant carbanions with the acrylate under Michael'saddition reaction conditions.

Example 3

Equimolar amounts of acid and DCC (dicyclocarbodiimide) were dissolvedin THF and stirred for an hour. To this stirred solution was addedpentaerythritol and catalytic amounts of DMAP and the reaction mixturewas stirred for 24 hours to get the product wherein n is O and R₁ is —H.

Example 4

90 mg of lithium aluminium hydride was suspended in 5 ml of anhydrousTHF under nitrogen atmosphere at 0° C. To this stirred suspension of LAHwas added a solution of 700 mg of phenol methyl ester drop-wise whilemaintaining the temperature at 0° C. After complete addition, thereaction mixture was allowed to warm to room temperature and stirred foranother 2 hours. After completion, the reaction was quenched by adding amixture of methanol and water and the product alcohol was isolated byextraction with ethyl acetate. The alcohol wherein n is 0 was dried andcharacterized by its spectral analysis.

Example 5

The compound shown above wherein n is 0 and R is H was prepared fromtrihydroxy benzene (phloroglucinol). Phloroglucinol was alkylated with,5-nitro, 2-phenol benzyl bromide by dissolving in acetone in thepresence of potassium carbonate.

The entire contents of each of the following are incorporated herein byreference.

-   Docket No.: 3805.1000-000; Provisional Patent Application No.    60/632,893, filed Dec. 3, 2004, now U.S. Pat. No. 7,678,877, Title:    Process For The Synthesis Of Polyalkylphenol Antioxidants, by    Suizhou Yang, et al;-   Docket No.: 3805.1000-003; U.S. Publication No.: 2006/0128929 A1    published Jun. 15, 2006; patent application Ser. No. 11/292,813    filed Dec. 2, 2005, Title: Process For The Synthesis Of    Polyalkylphenol Antioxidants, by Suizhou Yang, et al;-   Docket No.: 3805.1001-000; Provisional Patent Application No.    60/633,197, filed Dec. 3, 2004, Title: Synthesis Of Sterically    Hindered Phenol Based Macromolecular Antioxidants, by Ashish Dhawan,    et al.;-   Docket No.: 3805.1001-003; U.S. Publication No.: 2006/0128930 A1    published Jun. 15, 2006; patent application Ser. No. 11/293,050;    filed Dec. 2, 2005, Title: Synthesis Of Sterically Hindered Phenol    Based Macromolecular Antioxidants, by Ashish Dhawan, et al.;-   Docket No.: 3805.1002-000; Provisional Patent Application No.    60/633,252, filed Dec. 3, 2004, Title: One Pot Process For Making    Polymeric Antioxidants, by Vijayendra Kumar, et al.;-   Docket No.: 3805.1002-003; U.S. Publication No.: 2006/0128939 A1    published Jun. 15, 2006; patent application Ser. No. 11/293,049;    filed Dec. 2, 2005, Title: One Pot Process For Making Polymeric    Antioxidants, by Vijayendra Kumar, et al.;-   Docket No.: 3805.1003-000; Provisional Patent Application No.    60/633,196, filed Dec. 3, 2004, Title: Synthesis Of Aniline And    Phenol-Based Macromonomers And Corresponding Polymers, by Rajesh    Kumar, et al.;-   Docket No.: 3805.1003-003; U.S. Publication No.: 2006/0128931 A1    published Jun. 15, 2006, now U.S. Pat. No. 7,902,317; patent    application Ser. No.: 11/293,844; filed Dec. 2, 2005, Title:    Synthesis Of Aniline And Phenol-Based Macromonomers And    Corresponding Polymers, by Rajesh Kumar, et al.;-   Docket No.: 3805.1004-002; U.S. Publication No.: 2006/0041094 A1    published-   Feb. 23, 2006; patent application Ser. No. 11/184,724, filed Jul.    19, 2005, Title: Anti-Oxidant Macromonomers And Polymers And Methods    Of Making And Using The Same, by Ashok L. Cholli;-   Docket No.: 3805.1004-005; U.S. Publication No.: 2006/0041087 A1    published Feb. 23, 2006; patent application Ser. No. 11/184,716,    filed Jul. 19, 2005, Title: Anti-Oxidant Macromonomers And Polymers    And Methods Of Making And Using The Same, by Ashok L. Cholli;-   Docket No.: 3805.1005-003; U.S. Publication No.: 2006/0189824 A1    published Aug. 24, 2006, now U.S. Pat. No. 7,799,948; patent    application Ser. No. 11/360,020, filed Feb. 22, 2006, Title:    Nitrogen And Hindered Phenol Containing Dual Functional    Macromolecules Synthesis And Their Antioxidant Performances In    Organic Materials, by Rajesh Kumar, et al.-   Docket No.: 3805.1006-001; U.S. Publication No.: 2006/0233741 A1    published Oct. 19, 2006, now U.S. Pat. No. 7,705,185; U.S. patent    application Ser. No. 11/389,564, filed Mar. 24, 2006, Title:    Alkylated Macromolecular Antioxidants And Methods Of Making, And    Using The Same, by Rajesh Kumar, et al.-   Docket No.: 3805.1007-000; Provisional Patent Application No.    60/731,125, filed Oct. 27, 2005, Title: Macromolecular Antioxidants    And Polymeric Macromolecular Antioxidants, by Ashok L. Cholli, et    al.-   Docket No.: 3805.1008-000; Provisional Patent Application No.    60/731,021, filed Oct. 27, 2005, Title: Macromolecular Antioxidants    Based On Sterically Hindered Phenols And Phosphites, by Ashok L.    Cholli, et al.-   Docket No.: 3805.1009-000; Provisional Patent Application No.    60/742,150, filed Dec. 2, 2005, Title: Lubricant Composition, by    Kumar, Rajesh, et al.-   Docket No.: 3805.1010-000; Provisional Patent Application No.    60/731,325, filed Oct. 27, 2005, Title: Stabilized Polyolefin    Composition, by Kumar, Rajesh, et al.-   Docket No.: 0813.2006-003; U.S. Publication No.: 2005/0238789 A1    published Oct. 27, 2005, now U.S. Pat. No. 7,323,511; patent    application Ser. No. 11/040,193, filed Jan. 21, 2005, Title:    Post-Coupling Synthetic Approach For Polymeric Antioxidants, by    Ashok L. Choll, et al.;-   Docket No.: 0813.2006-002; WO Publication No.: WO/2005/070974    published Aug. 4, 2005; Patent Application No.: PCT/US2005/001948,    filed Jan. 21, 2005, Title: Post-Coupling Synthetic Approach For    Polymeric Antioxidants, by Ashok L. Cholli et al.;-   Docket No.: 0813.2002-008; WO Publication No.: WO/2005/071005    published Aug. 5, 2005; Patent Application No.: PCT/US2005/001946,    filed Jan. 21, 2005, Title: Polymeric Antioxidants, by Ashok L.    Choll, et al.;-   Docket No.: 0813.2002-006; WO Publication No.: WO/2003/087260    published Oct. 23, 2003; Patent Application No.: PCT/US03/10782,    filed Apr. 4, 2003, Title: Polymeric Antioxidants, by Ashok L.    Choll, et al.;-   Docket No.: 0813.2002-004; U.S. Publication No.: 2004/0214935 A1    published Oct. 28, 2004, now U.S. Pat. No. 7,595,074; patent    application Ser. No. 10/761,933, filed Jan. 21, 2004, Title:    Polymeric Antioxidants, by Ashish Dhawan, et al.;-   Docket No.: 0813.2002-001; U.S. Publication No.: 2003/0230743 A1    published Dec. 18, 2003, now U.S. Pat. No. 7,233,432; patent    application Ser. No.: 10/408,679, filed Apr. 4, 2003, Title:    Polymeric Antioxidants, by Ashok L. Choll, et al.;-   U.S. Pat. No. 6,770,785 B1-   U.S. Pat. No. 5,834,544-   Neftekhimiya (1981), 21(2): 287-298.

While this invention has been particularly shown and described withreferences to preferred embodiments thereof, it will be understood bythose skilled in the art that various changes in form and details may bemade therein without departing from the scope of the invention.

EQUIVALENTS

Those skilled in the art will recognize, or be able to ascertain usingno more than routine experimentation, many equivalents to specificembodiments of the invention described specifically herein. Suchequivalents are intended to be encompassed in the scope of the followingclaims.

1.-62. (canceled)
 63. A method of inhibiting oxidation in an oxidizable material comprising combining the oxidizable material with a compound represented by the following structural formula:

wherein: R is:

A in each occurrence, independently is —O—, —NH—, —S—, —C(O)—, —C(O)NH—, —NHC(O)—, —C(O)O—, —OC(O)—, —CH═N— or —N═CH—; A′ in each occurrence, independently is a bond, —O—, —NH—, —S—, —C(O)—, —C(O)NH—, —NHC(O)—, —C(O)O—, —OC(O)—, —CH═N— or —N═CH—; B in each occurrence, independently is a bond or an optionally substituted alkylene group; C in each occurrence independently is —H, an optionally substituted alkylene group or

R₁ and R₂ in each occurrence, independently is an optionally substituted alkyl, optionally substituted aryl or optionally substituted aralkyl; Z in each occurrence, independently is a bond, an optionally substituted alkylene group, —(CH₂)₁NHC(O)(CH₂)₁—, —(CH₂)₁C(O)NH(CH₂)₁—, —(CH₂)₁C(O)O(CH₂)₁—, —(CH₂)₁OC(O)(CH₂)₁—, —(CH₂)₁CH═N(CH₂)₁—, —(CH₂)₁N═CH(CH₂)₁—, —(CH₂)₁NH(CH₂)₁—, —(CH₂)₁S(CH₂)₁—, —(CH₂)₁O(CH₂)₁— or —(CH₂)₁C(O)(CH₂)₁—; i in each occurrence, independently is 0, 1, 2 or 3; j in each occurrence, independently is 0, 1, 2, 3 or 4; l in each occurrence, independently is 0 or a positive integer from 1 to 12; s is a positive integer from 1 to 6; comprising the step of combining R*, wherein R* is:

with X′″, wherein X′″ is represented by the following structural formula: and

A″ is NO₂, NH₂ or OH; Q is —OH; D is halogen, haloalkyl, —(CH₂)₁—NHC(O)—F, —(CH₂)₁—C(O)NH—F, —(CH₂)₁—C(O)O—F, —(CH₂)₁—OC(O)—F, —(CH₂)₁—CH═N—F, —(CH₂)₁—N═CH—F, —(CH₂)₁₀—F or —(CH₂)₁—C(O)—F; and F in each occurrence, independently is —H, halogen, haloalkyl or an aliphatic group; to produce Y, wherein Y is represented by the following structural formula:

wherein: Q′ is —O—; D″ is a bond, alkylene, —(CH₂)₁—NHC(O)—F″, —(CH₂)₁—C(O)NH—F″, —(CH₂)₁—C(O)O—F″, —(CH₂)₁—OC(O)—F″, —(CH₂)₁—CH═N—F″, —(CH₂)₁—N═CH—F″, —(CH₂)₁—NH—F″, —(CH₂)₁—S—F, —(CH₂)₁O—F″ or —(CH₂)₁—C(O)—F″; and F″ in each occurrence, independently is absent or bivalent aliphatic group.
 64. The method of claim 63, wherein D is halogen or haloalkyl.
 65. The method of claim 64, wherein X′″ is:


66. The method of claim 65, wherein R* is:


67. The method of claim 66, wherein the method further comprises the step of combining Y with U, wherein U is represented by the following structural formula:

wherein: G is —COOH or COOalkyl; to produce the macromonomer.
 68. The method of claim 67, wherein U is:


69. The method of claim 68, wherein the macromonomer is represented by the following structural formula:


70. A method of inhibiting oxidation in an oxidizable material comprising combining the oxidizable material with a compound represented by the following structural formula:

wherein: A is —C(O)NR′—, —NR′C(O)—, —NR′—, —CR′═N—, —C(O)—, —C(O)O—, —OC(O)—, —O—, —S—, —C(O)OC(O)— or a bond; each R′ is independently —H or optionally substituted alkyl; each R** is independently an optionally substituted alkyl, optionally substituted aryl, optionally substituted alkoxycarbonyl, optionally substituted ester, —OH, —NH₂, —SH, or

each R₁ and R₂ is independently an optionally substituted alkyl, optionally substituted aryl, optionally substituted alkoxycarbonyl, optionally substituted ester, —OH, —NH₂ or —SH; X is —C(O)O—, —OC(O)—, —C(O)NR′—, —NR′C(O)—, —NR′—, —C(O)—, —O—, —S—, —NR′— or —C(O)OC(O)—; M is —H, an alkyl or

each n is independently a positive integer from 1 to 6; each m is independently 0 or a positive integer from 1 to 6; and each s, q and u are independently integers from 0 to
 4. 71. The method of claim 70, wherein: A is —C(O)O—, —OC(O)—, —C(O)NH—, —NHC(O)—, —NH—, —O— or —C(O)—; R′ is —H; each R** is independently an optionally substituted alkyl or optionally substituted alkoxycarbonyl; each R₂ is independently an optionally substituted alkyl; X is —O—; M is —H or an alkyl; each n is independently integers from 1 to 4; each m is independently integers from 0 to 4; and each s and q are independently integers from 0 to
 2. 72. The method of claim 71, wherein: A is —C(O)NH— or —NHC(O)—; each R** is independently an alkyl or an alkoxycarbonyl; each R₂ is independently an alkyl; and s is
 2. 73. The method of claim 72, wherein each R** is independently an alkyl group.
 74. The method of claim 73, wherein each R** is independently a tert-butyl group.
 75. The method of claim 74, wherein both R** are ortho to the —OH group.
 76. A method of inhibiting oxidation in an oxidizable material comprising combining the oxidizable material with a compound represented by the following structural formula:


77. A method of inhibiting oxidation in an oxidizable material comprising combining the oxidizable material with a compound represented by the following structural formula:

wherein n=1 to
 4. 78. A method of making a compound represented by the following Structural Formula:

wherein: A is —C(O)NR′—, —NR′C(O)—, —NR′—, —C(O)—, —C(O)O—, —OC(O)—, —O—, —S—, —C(O)OC(O)— or a bond; each R′ is independently —H or optionally substituted alkyl; each R** is independently an optionally substituted alkyl, optionally substituted aryl, optionally substituted alkoxycarbonyl, optionally substituted ester, —OH, —NH₂, —SH, or

each R₁ and R₂ is independently an optionally substituted alkyl, optionally substituted aryl, optionally substituted alkoxycarbonyl, optionally substituted ester, —OH, —NH₂ or —SH; X is —C(O)O—, —OC(O)—, —C(O)NR′—, —NR′C(O)—, —NR′—, —CH═N—, —C(O)—, —O—, —S—, —NR′— or —C(O)OC(O)—; M is —H, an alkyl or

each n is independently a positive integer from 1 to 6; each m is independently 0 or a positive integer from 1 to 6; and each s, q and u are independently integers from 0 to 4; comprising the steps of: a) combining G, wherein G is represented by the following structural formula:

wherein g is a phenolic acid with H, wherein H is represented by the following structural formula:


79. A method of making a compound represented by the following Structural Formula: R—Z—(CH₂)_(k)—Z—R wherein R is:

A is —C(O)NR′—, —NR′C(O)—, —NR′—, —CR′═N—, —C(O)—, —C(O)O—, —OC(O)—, —O—, —S—, —C(O)OC(O)— or a bond; Z in each occurrence, independently is a bond, an optionally substituted alkylene group, —(CH₂)₁NHC(O)(CH₂)₁—, —(CH₂)₁C(O)NH(CH₂)₁—, —(CH₂)₁C(O)O(CH₂)₁—, —(CH₂)₁OC(O)(CH₂)₁—, —(CH₂)₁CH═N(CH₂)₁—, —(CH₂)₁N═CH(CH₂)₁—, —(CH₂)₁NH(CH₂)₁—, —(CH₂)₁S(CH₂)₁—, —(CH₂)₁O(CH₂)₁— or —(CH₂)₁C(O)(CH₂)₁—; each R′ is independently —H or optionally substituted alkyl; each R** is independently an optionally substituted alkyl, optionally substituted aryl, optionally substituted alkoxycarbonyl, optionally substituted ester, —OH, —NH₂, —SH, or

each R₁ and R₂ is independently an optionally substituted alkyl, optionally substituted aryl, optionally substituted alkoxycarbonyl, optionally substituted ester, —OH, —NH₂ or —SH; X is —C(O)O—, —OC(O)—, —C(O)NR′—, —NR′C(O)—, —NR′—, —CR′═N—, —C(O)—, —O—, —S—, —NR′— or —C(O)OC(O)—; each M′ is independently —H, alkyl, or

each n is independently a positive integer from 1 to 6; each m is independently 0 or a positive integer from 1 to 6; l in each occurrence, independently is 0 or a positive integer from 1 to 12; and k in each occurrence independently is a positive integer from 1 to 12; each q is independently an integer from 0 to 3; each s, and u are independently integers from 0 to 4; and r is an integer from 0 to 4; comprising the steps of: a) polymerizing a compound represented by the following structural formula:

and b) isolating the polymer.
 80. The method of claim 79, wherein R is:

and wherein the resulting polymer is:


81. The method of claim 79, wherein R is:

wherein n=1 to 4; and wherein the resulting polymer is: 